This program represents a continuation of long-term studies on the metabolism of normal and neoplastic tissues, with the purpose of understanding the enzymatic and metabolic basis of tumor cell growth and proliferation. Our studies of recent years have demonstrated marked alterations of enzyme activity and isozyme composition in chemically induced, transplantable hepatomas, which appear to provide important clues to tumor cell behavior, and which emphasize an important role of phosphate dynamics and turn over in tumor cell regulation. To pursue this problem further, we are exploring the prevalence, enzymatic activity and isozyme composition of two enzymes that can, on the basis of current knowledge, be presumed to affect the levels of inorganic phosphate, pyrophosphate and the purine nucleotides. These are creatine kinase (EC 2.7.3.2) and inorganic pyrophosphatase (EC 3.6.1.1). Experimental materials for this study are normal adult and fetal tissues, including regenerating liver of the rat and mouse, and a variety of solid tumors and culture ascites cells of the same species.